1. Field of the Invention
The present invention relates generally to infectious diseases and, more particularly, to the diagnosis of chronic Pseudomonas aeruginosa infection especially as associated with cystic fibrosis.
Cystic fibrosis (CF) is the most common lethal genetic syndrome among Caucasians. In the United States, the incidence is 1 in 2,000 live births. CF is a generalized metabolic disorder involving change in the serous and mucous secretions resulting in, among other symptoms, progressive obstructive pulmonary disease and malabsorption due to pancreatic enzyme insufficiency. As late as the 1950's, life expectancy for cystic fibrosis patients was extremely short. Even today, only half of CF patients reach their 20th birthday.
Pulmonary complications associated with progressive obstructive pulmonary disease are responsible for the majority of morbidity and virtually all mortality in afflicted patients. Pulmonary infections are generally a fact of life for the CF patient. The majority of these infections are caused by the gram-negative bacterium Pseudomonas aeruginosa (PA). Once established in CF patients, PA is an extremely difficult organism to eradicate. The majority of CF patients are chronically infected with PA.
Treatment of chronic PA infection with antibiotics, including the aminoglycosides, generally fails to eradicate PA. Indeed, some researchers believe that the continuous use of antibiotics actually contributes to the bacteria's persistence. It is not uncommon to find patients infected with
strains resistant to all known antibiotics. These patients often have an unrelenting deterioration of pulmonary function ultimately leading to death. A recent study reported survival rates to age 16 years in CF afflicted children with and without chronic PA infection. The researchers reported a 53% survival rate in infected children versus an 84% survival rate in non-infected children.
Recent advances in the treatment of gram-negative bacterial infections, particularly PA infections, provide hope for CF patients with chronic PA infections. Methods employing monoclonal antibody compositions, such as those disclosed in U.S. patent application Ser. No. 855,878, appear particularly promising. Before any therapy can be effective, however it is important to accurately diagnose the nature of the infection. Once diagnosed, it is extremely beneficial to follow the effectiveness of therapy throughout its course. There is therefore a need for compositions and methods useful in the diagnosis of chronic PA infection and in following the course of such infection.
2. Discussion of the Relevant Literature
U.S. Pat. No. 4,587,121 discloses the use of hyperimmune serum globulin having high titers of antibody against all seven Fisher Immunotypes of Pseudomonas aeruginosa for use in treating patients with Pseudomonas infection.
Rowe and Meadow, Eur. J. Biochem. (1983) 132:329-37, report the isolation of lipopolysaccharides from Pseudomonas aeruginosa strain PAC1R and its lipopolysaccharide-defective mutants.
Meadow et al., J. Gen. Microbio. (1984) 130:631-44, describe the characterization of surface antigens in Pseudomonas aeruginosa.
Appelmelk et al., J. Immuno. Meth. (1985) 82:199-207, describe an enzyme linked immunosorbant assay (ELISA) for the measurement of antibodies to different parts of gram-negative lipopolysaccharide core region employing core antigens of E. coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A.
Gascon et al., 25th ICAAC, Minneapolis, Minn., (1985) Abstract No. 77, describe the functional activity of monoclonal antibodies against common core lipopolysaccharide antigen of P. aeruginosa.
Poxton et al., FEMS Microbiology Letter (1985) 27:247-51, describe the association on SDS-polyacrylamide gels of lipopolysaccharide and outer membrane proteins of P. aeruginosa as revealed by monoclonal antibodies and Western blotting employing P. aeruginosa Habs serotypes 1 and 4.
Wilmott et al., AJDC (1985) 139:669-71 report cystic fibrosis survival rates and the influences of allergy and Pseudomonas aeruginosa.